Background

Gene therapy strategies have exploited lenti or retro viral approaches for long-term gene replacement, however, their clinical applications remain limited because of potential for viral-associated oncogenesis. Recently, gene therapy strategies have attempted to use hybrid Adenovirus/Adeno-associated viruses (Ad/AAV) to combine the capacity, tropism and ease of production of adenovirus (Ad) with adeno-associated virus (AAVs) ability for site-specific integration (SSI). Although the AAV Rep78 protein is required for SSI, it also has an inhibitory effect on Ad replication, particularly when co-expressed within the Ad backbone leading difficulty in generating and integrating transgene within the back-bone of a single hybrid virus.

Technology

Researchers at Stony Brook University have identified a genetic element within the Rep gene sequence, which is inhibitory to Ad replication. This AAV Rep gene was then genetically recoded using synonymous codon pair re-engineering to overcome Reps inhibitory effects on Ad replication. The novel construct thus created provides a unique opportunity to place all genetic elements in one virus for the purpose of safely integrating a transgene into a specific region of the human genome.

Advantages

Combines the advantages of Ad (high titer, high infectivity and large capacity) and integration capability of AAV Offers one-step packaging systems for rAAV viral production.

Application

New Gene therapy vectors Improved rAAV production methods.